DESCRIPTION (Adapted from applicant's description): Wiskott-Aldrich syndrome (WAS) is an X chromosome-linked immunodeficiency. This disease is life-threatening. Most untreated children die in the first decade of life. The gene responsible for this disorder, WASP, has been recently isolated. However, physiological roles of the gene product, Wiskott-Aldrich syndrome protein (WASP), are not well understood. The goal of the proposed study is to understand physiological functions of WASP. WASP is a hematopoietic cell-specific protein whose C-terminal region exhibits the activity to regulate actin polymerization. However, functions of the N-terminus of WASP are still unknown. The investigator has identified Calcium-Integrin-Binding-protein (CIB) as a WASP binding protein by yeast two-hybrid screening. CIB interacts with the PH domain of WASP N-terminus; CIB has been recently isolated as a protein which binds to integrin alpha II b, beta 3; CIB is N-myristoylated to bind to plasma membrane. Based on these findings, it is hypothesized that WASP is recruited to plasma membrane by binding of its PH domain to CIB and plays important roles in cell adhesion, cytoskeleton functions or cellular signaling. The following specific aims are proposed. 1) To demonstrate that WASP is recruited to plasma membrane by binding of its PH domain to CIB. 2) To determine whether CIB and WASP interact in MEG-Ol human megakaryoblastic cells and such interaction is required for cytoskeletal organization, integrin function, and megakaryocyte differentiation.